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Interleukin-7 and Toll-Like Receptor 7 Induce Synergistic B Cell and T Cell Activation

OBJECTIVES: To investigate the potential synergy of IL-7-driven T cell-dependent and TLR7-mediated B cell activation and to assess the additive effects of monocyte/macrophages in this respect. METHODS: Isolated CD19 B cells and CD4 T cells from healthy donors were co-cultured with TLR7 agonist (TLR7...

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Autores principales: Bikker, Angela, Kruize, Aike A., van der Wurff-Jacobs, Kim M. G., Peters, Rogier P., Kleinjan, Marije, Redegeld, Frank, de Jager, Wilco, Lafeber, Floris P. J. G., van Roon, Joël A. G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989236/
https://www.ncbi.nlm.nih.gov/pubmed/24740301
http://dx.doi.org/10.1371/journal.pone.0094756
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author Bikker, Angela
Kruize, Aike A.
van der Wurff-Jacobs, Kim M. G.
Peters, Rogier P.
Kleinjan, Marije
Redegeld, Frank
de Jager, Wilco
Lafeber, Floris P. J. G.
van Roon, Joël A. G.
author_facet Bikker, Angela
Kruize, Aike A.
van der Wurff-Jacobs, Kim M. G.
Peters, Rogier P.
Kleinjan, Marije
Redegeld, Frank
de Jager, Wilco
Lafeber, Floris P. J. G.
van Roon, Joël A. G.
author_sort Bikker, Angela
collection PubMed
description OBJECTIVES: To investigate the potential synergy of IL-7-driven T cell-dependent and TLR7-mediated B cell activation and to assess the additive effects of monocyte/macrophages in this respect. METHODS: Isolated CD19 B cells and CD4 T cells from healthy donors were co-cultured with TLR7 agonist (TLR7A, Gardiquimod), IL-7, or their combination with or without CD14 monocytes/macrophages (T/B/mono; 1 : 1 : 0,1). Proliferation was measured using (3)H-thymidine incorporation and Ki67 expression. Activation marker (CD19, HLA-DR, CD25) expression was measured by FACS analysis. Immunoglobulins were measured by ELISA and release of cytokines was measured by Luminex assay. RESULTS: TLR7-induced B cell activation was not associated with T cell activation. IL-7-induced T cell activation alone and together with TLR7A synergistically increased numbers of both proliferating (Ki67(+)) B cells and T cells, which was further increased in the presence of monocytes/macrophages. This was associated by up regulation of activation markers on B cells and T cells. Additive or synergistic induction of production of immunoglobulins by TLR7 and IL-7 was associated by synergistic induction of T cell cytokines (IFNγ, IL-17A, IL-22), which was only evident in the presence of monocytes/macrophages. CONCLUSIONS: IL-7-induced CD4 T cell activation and TLR7-induced B cell activation synergistically induce T helper cell cytokine and B cell immunoglobulin production, which is critically dependent on monocytes/macrophages. Our results indicate that previously described increased expression of IL-7 and TLR7 together with increased numbers of macrophages at sites of inflammation in autoimmune diseases like RA and pSS significantly contributes to enhanced lymphocyte activation.
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spelling pubmed-39892362014-04-21 Interleukin-7 and Toll-Like Receptor 7 Induce Synergistic B Cell and T Cell Activation Bikker, Angela Kruize, Aike A. van der Wurff-Jacobs, Kim M. G. Peters, Rogier P. Kleinjan, Marije Redegeld, Frank de Jager, Wilco Lafeber, Floris P. J. G. van Roon, Joël A. G. PLoS One Research Article OBJECTIVES: To investigate the potential synergy of IL-7-driven T cell-dependent and TLR7-mediated B cell activation and to assess the additive effects of monocyte/macrophages in this respect. METHODS: Isolated CD19 B cells and CD4 T cells from healthy donors were co-cultured with TLR7 agonist (TLR7A, Gardiquimod), IL-7, or their combination with or without CD14 monocytes/macrophages (T/B/mono; 1 : 1 : 0,1). Proliferation was measured using (3)H-thymidine incorporation and Ki67 expression. Activation marker (CD19, HLA-DR, CD25) expression was measured by FACS analysis. Immunoglobulins were measured by ELISA and release of cytokines was measured by Luminex assay. RESULTS: TLR7-induced B cell activation was not associated with T cell activation. IL-7-induced T cell activation alone and together with TLR7A synergistically increased numbers of both proliferating (Ki67(+)) B cells and T cells, which was further increased in the presence of monocytes/macrophages. This was associated by up regulation of activation markers on B cells and T cells. Additive or synergistic induction of production of immunoglobulins by TLR7 and IL-7 was associated by synergistic induction of T cell cytokines (IFNγ, IL-17A, IL-22), which was only evident in the presence of monocytes/macrophages. CONCLUSIONS: IL-7-induced CD4 T cell activation and TLR7-induced B cell activation synergistically induce T helper cell cytokine and B cell immunoglobulin production, which is critically dependent on monocytes/macrophages. Our results indicate that previously described increased expression of IL-7 and TLR7 together with increased numbers of macrophages at sites of inflammation in autoimmune diseases like RA and pSS significantly contributes to enhanced lymphocyte activation. Public Library of Science 2014-04-16 /pmc/articles/PMC3989236/ /pubmed/24740301 http://dx.doi.org/10.1371/journal.pone.0094756 Text en © 2014 Bikker et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bikker, Angela
Kruize, Aike A.
van der Wurff-Jacobs, Kim M. G.
Peters, Rogier P.
Kleinjan, Marije
Redegeld, Frank
de Jager, Wilco
Lafeber, Floris P. J. G.
van Roon, Joël A. G.
Interleukin-7 and Toll-Like Receptor 7 Induce Synergistic B Cell and T Cell Activation
title Interleukin-7 and Toll-Like Receptor 7 Induce Synergistic B Cell and T Cell Activation
title_full Interleukin-7 and Toll-Like Receptor 7 Induce Synergistic B Cell and T Cell Activation
title_fullStr Interleukin-7 and Toll-Like Receptor 7 Induce Synergistic B Cell and T Cell Activation
title_full_unstemmed Interleukin-7 and Toll-Like Receptor 7 Induce Synergistic B Cell and T Cell Activation
title_short Interleukin-7 and Toll-Like Receptor 7 Induce Synergistic B Cell and T Cell Activation
title_sort interleukin-7 and toll-like receptor 7 induce synergistic b cell and t cell activation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989236/
https://www.ncbi.nlm.nih.gov/pubmed/24740301
http://dx.doi.org/10.1371/journal.pone.0094756
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